ANTIBIOTIC THERAPY IN THE INTENSIVE CARE

UNITDr amrita

Moderator : dr amit rastogi

THE ACTION OF ANTIMICROBIAL DRUGS

Figure 20.2

PROTEIN SYNTHESIS INHIBITORS

Figure 20.4

BETA LACTAMS

• Narrow spectrum

• Narrow spectrum pEnicillinase susceptible. Penicillin

• Very-narrow-spectrum penicillinase-resistant drugs

• Methicillin

• Nafacillin

• Oxacillin

• Wide spectrum

• Wider-spectrum penicillinase-susceptible drugs

• Ampicillin and amoxicillin.

• Piperacillin and ticarcillin.

• Wide spectrum pEnicillinase resistant drugs

• Carbapenem

• Imipinem

• Meropenem

• Doripinem

• Ertapenem

THE CEPHALOSPORIN FAMILY

OTHER CELL WALL INHIBITORS

• Monobactams

• Aztreonams

• Vancomycin

• Telavancin

• Dalacin

• teichoplanin

AMINOGLYCOSIDES

• Gentamycin

• Tobramcin

• Amikacin

• Toxicity profile

• Ototoxicity

• Nephrotoxicity

• Blocking neuromuscular transmission

• hypersensitivity

PROTEIN SYNTHESIS INHIBITORS

• Linezolid

• Quinupristin/Dalfopristin

• Daptomycin

• Tigecycline

ANTIMICROBIALS WITH ACTIVITY AGAINST ANAEROBES

• Metronidazole

• clindamycin

PHARMACOKINETICS AND PHARMACODYNAMICS OF ANTIBIOTICS

SPECIAL CONSIDERATIONS IN THE CRITICALLY ILL PATIENT

• Volume of distribution

• Metabolism

• Clearance : ranal hyper and hypo filtration

• hypoalbunaemia

HOW TO START

• Loading dose = target plasma conc * volume of distribution

• High loading doses for hydrophilic drugs like beta lactams , vancomycin , and

aminoglycosides

• Lipophilic drugs like macrolides,linezolid,tetracyclins do not require a high loading

dose

• Renal and hepatic function do not affect loading dose

PHARMACOKINETIC AND PHARMACODYNAMICS PROPERTIES OF ANTIBIOTICS

• Minimum inhibitory concentration : The MIC is the lowest concentration of an

antibiotic that completely inhibits the growth of a microorganism in vitro. While the

MIC is a good indicator of the potency of an antibiotic, it indicates nothing about the

time course of antimicrobial activity

• Parameters quantifying serum level :

• Peak serum level : Cmax

• Trough level : Cmin

• Area Under the serum concentration time Curve (AUC) : indicates the amount of drug

PARAMETERS INDICATING ANTIBIOTIC ACTIVITY

• he Peak/MIC ratio, Cpmax divided by the MIC.

• the T>MIC, percentage of a dosage interval in which the serum level exceeds the

MIC.

• and the 24h-AUC/MIC ratio. determined by dividing the 24-hour-AUC by the MIC

Pattern of Activity Antibiotics Goal of Therapy PK/PD Parameter

Type I

Concentration-dependent killing and

Prolonged persistent effects

Aminoglycosides

Daptomycin

Fluoroquinolones

Ketolides

Maximize concentrations24h-AUC/MIC

Peak/MIC

Type II

Time-dependent killing and

Minimal persistent effects

Carbapenems

Cephalosporins

Erythromycin

Linezolid

Penicillins

Maximize duration of exposure T>MIC

Type III

Time-dependent killing and

Moderate to prolonged persistent effects.

Azithromycin

Clindamycin

Oxazolidinones

Tetracyclines

Vancomycin

Maximize amount of drug 24h-AUC/MIC

DOSING OF A CONCENTRATION DEPENDANT ANTIBIOTIC

DOSING OF A TIME DEPENDANT ANTIBIOTIC

• Multiple small dosing to obtain the

maximum t > MIC

• Role of prolonged infusions

ANTIBIOTIC RESISTANCE

• Common mechanisms

• Impermeability of the drug:

• alteration in target molecules

• enzymatic drug modifications

• Efflux

• both chromosomal mutations or genetic transfer ( plasmids ) can be responsible for

the resistance acquisition,

FACTORS RESPONSIBLE FOR ANTIBIOTIC RESISTANCE

• Lack of education

• Hospital acquired infections

• Use of antibiotics in agriculture or aquaculture

• Environmental factors

• Use in household products

SOME COMMON RESISTANT STRAINS : GRAM POSITIVE

• Methicillin resistant Staplylococcus aureus (MRSA)

• Vancomycin intermediate staph. Aureus ( VISA )

• Enterococcus- HLAR

• Multi drug resistant strep pneumoniae

SOME COMMON RESISTANT STRAINS : GRAM NEGATIVE

• Extended-Spectrum b-Lactamase –Producing Enterobacteriaceae

• Antibiotic options carbapenems,

• tigecycline

• Carbapenemase producing enterobacteriaciae

• The delhi metalloprotease

• No susceptibility to any beta lactam or other higher antibiotics

• Susceptible to tigecycline and colistin

• Multi drug resistant pseudomonas MDR P aeruginosa are strains that are

resistant to 2 or more classes of antibiotics

• Antipseudomonal Penicillins with or with out beta lactamases

• Piperacillin tazobactum

• Ticarcillin

• Aztreonam

• Caeftazidime in combination with aminoglycosides

• Carbapenems : imipinem > doripinem > meropenem.etrapenem has no role against

pseudomonas.

• colistin

ANTIBIOTIC THERAPY IN THE ICU

ANTIBIOTIC STEWARDSHIP

• The Centers for Disease Control and Prevention (CDC) estimates more than two

million people are infected with antibiotic-resistant organisms, resulting in

approximately 23,000 deaths annually.

• Has recommended the setting up of special bodies in all acute care hospitals for the

optimization of antibiotic use-called antibiotic stewardship programmes.

SPECIFIC INTERVENTIONS TO IMPROVE ANTIBIOTIC USE

• formal procedure for all clinicians to review the appropriateness of all antibiotics 48

hours after the initial orders (e.g. antibiotic time out)

• specified antibiotic agents need to be approved by a physician or pharmacist prior to

dispensing

• physician or pharmacist to review courses of therapy for specified antibiotic agents

(i.e., prospective audit with feedback)

• Automatic changes from intravenous to oral antibiotic therapy in appropriate

situations

• Dose adjustments in cases of organ dysfunction

• Dose optimization (pharmacokinetics/pharmacodynamics) to optimize the treatment

of organisms with reduced susceptibility

• Automatic alerts in situations where therapy might be unnecessarily duplicative

• Time-sensitive automatic stop orders for specified antibiotic prescriptions

• track rates of C. difficile infection

• Monitor total amounts of antibiotics used

ANTIBIOTIC STRATEGIES TO COMBAT RESISTANCE

Blast them

Fool them

Stop irritating them.

ANTIBIOTIC STRATEGY FOR SKIN AND SOFT TISSUE INFECTION

ANTIBIOTIC STRATEGY FOR COMMUNITY ACQUIRED PNEUMONIA

• A b-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam)

azithromycin (level II evidence) or a respiratory fluoroquinolone

• If Pseudomonas is a consideration

• An antipneumococcal, antipseudomonal b-lactam (piperacillintazobactam,

cefepime, imipenem, or meropenem) plus

• either ciprofloxacin or levofloxacin (750 mg)

+

• Or

• The above b-lactam plus an aminoglycoside and azithromycin

• or

• The above b-lactam plus an aminoglycoside and an antipneumococcal

fluoroquinolone (for penicillin-allergic patients,

substitute aztreonam for above b-lactam)

ANTIBIOTIC INFECTION FOR INTRA ABDOMINAL INFECTIONS